With the increased use of noninvasive neuroimaging, there has been an increase in the detection of brain arteriovenous malformations prior to symptomatic bleeding, but there is currently no clear consensus for the management of these lesions. Patients diagnosed with unruptured or asymptomatic arteriovenous malformations may be managed conservatively or, alternatively, they may be offered interventional therapy with the aim of obliterating the origin of the arteriovenous malformation. Several interventional therapies, including neurosurgery, embolization, and stereotactic radiotherapy have been used successfully in these patients, but there is little clinical evidence to guide the choice of interventional therapy, or to demonstrate its superiority over conservative management. A prospective population-based cohort study in Scotland previously showed that patients receiving interventional therapy for arteriovenous malformation had worse outcomes than those who did not (Lancet Neurol 2008 Mar;7(3):223). Now, a randomized trial compares the addition of interventional therapy to medical management vs. medical management alone in adults with unruptured arteriovenous malformation.

A total of 226 adults (mean age 45 years) with unruptured brain arteriovenous malformation were randomized to medical management alone vs. medical management plus interventional therapy. Patients, clinicians, and investigators were aware of treatment assignment. Medical management consisted of pharmacologic therapy for existing medical disorders (such as seizures or headaches) or any coexisting vascular risk factors (such as diabetes or arterial hypertension), as needed. Patients randomized to interventional therapy additionally received neurosurgery, embolization, or stereotactic radiotherapy, either alone or in combination, at the discretion of the local trial investigator. Patients with evidence of recent or prior hemorrhage, or who had received previous interventional therapy for brain arteriovenous malformation, were excluded from the trial. The goal of the interventional therapy was complete eradication of the arteriovenous malformation. The primary outcome was a composite of symptomatic stroke or death.

The trial was stopped early by an independent data and safety monitoring board, due to superiority of medical management alone based on a prespecified stopping value for the primary outcome. The interim analysis included 223 patients (99% of those randomized) with a median follow-up of 33 months. Symptomatic stroke or death occurred in 10% of those receiving medical management alone vs. 31% of those receiving interventional therapy plus medical management (p < 0.05, NNT 5). The incidence of stroke was 11% with medical management alone vs. 39% with interventional therapy plus medical management (p < 0.0001, NNT 4). In addition, neurologic deficits unrelated to stroke occurred in 0.9% of those treated with medical management alone vs. 12% of those treated with interventional therapy plus medical management (p = 0.0008, NNT 9).

The results of this trial extend previous findings from an observational study, and further support the conclusion that current interventional therapies for unruptured arteriovenous malformations do not improve cerebrovascular outcomes. However, arteriovenous malformations are associated with a long natural history, and the median follow-up of 33 months included in this trial limits the ability to make conclusions about long-term effectiveness. In addition, by not including patients who had received previous interventional therapy for brain arteriovenous malformation, patients with a more aggressive disease course may have been excluded, and this may therefore limit the generalizability of the findings.